A human cell-based SARS-CoV-2 vaccine elicits potent neutralizing antibody responses and protects mice from SARS-CoV-2 challenge

ABSTRACT

To curb the pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple platforms have been employed toward a safe and highly effective vaccine. Here, we develop a novel cell-based vaccine candidate, namely K562-S, by utilizing human cell K562 as a cellular carrier to display Spike (S) protein of SARS-CoV-2 on the membrane. Analogous to the traditional inactivated vaccine, K562-S cells can be propagated to a large scale by culturing and completely lose their viability after exposure to X-ray irradiation or formalin. We in turn demonstrated high immunogenicity of formalin-inactivated K562-S vaccine in both mouse and non-human primates and its protective efficacy in mice. In mice, immunization with inactivated K562-S vaccines can elicit potent neutralizing antibody (nAb) responses persisting longer than 5 months. We consequently showed in a hACE2 mouse model of SARS-CoV-2 infection that a two-shot vaccination with adjuvanted K562-S rendered greater than 3 log reduction in viral lung load and concomitant ameliorated lung pathology. Of importance, the administration of the same regimen in non-human primates was able to induce a neutralizing antibody titer averaging three-fold higher relative to human convalescent serum. These results together support the promise of K562-based, S-protein-expressing vaccines as a novel vaccination approach against SARS-CoV-2. Importantly, with a powerful capacity to carry external genes for cell-based vectors, this platform could rapidly generate two- and multiple-valent vaccines by incorporating SARS-CoV-2 mutants, SARS-CoV, or MERS-CoV.

KEYWORDS:

• SARS-CoV-2
• cell-based vaccines
• K562-S
• mouse model
• non-human primate model
• neutralizing antibody
• protection

Acknowledgments

We thank the members of the J.X. and X.Z. laboratory for discussion and help with experiments. J.X. conceived the study. J.X., X.Z., C.Z., P.Z., Z.Q. X.H., L.D., K.C., H.P. designed the experiments. X.H., L.D., K.C., H.P. performed the experiments. C.G., Y.L. Y.X. developed and performed the authentic neutralization assay. D.L., C.Z. and S.S. help the histopathologic experiments. X.H., X.W., M.F., Z.Z. W.C. and J.Z. support the animal experiments. C.Q. helps the single-cell soring by flow cytometry. X.H. and C.Z. analyzed the data and wrote the manuscript. J.X., X.Z. and C.Z. provided supervision and oversaw final manuscript preparation. All authors reviewed and approved the version for publication.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Competing interests

J.X., X.Z., X.H., L.D. and K.C. are inventors on patent application (Chinese Application No. 202010544616.0) submitted by Shanghai Public Health Clinical Center that covers the use of SARS-CoV-2 vaccines K562-S.

Data and materials availability

All data are available in the main text or the supplementary materials.

Additional information

Funding

J.X. are supported by National Natural Science Foundation of China (81672018, 81761128007, 82071788). J.X. and X.Z. are supported by National 13th Five-Year Grand Program on Key Infectious Disease Control (2017ZX10202102, 2018ZX10301403-003). C.Z. is supported by Shanghai Pujiang Program (19PJ1409100). X.Z. is supported by Shanghai Science and Technology Commission (18DZ2293000). P.Z. is supported by the National Key Research and Development Program of China (2016YFC1200401).